pivotal study to assess the efficacy, safety and tolerability of dupilumab in patients with moderate-to-severe copd with type 2 inflammation

Conditions: Chronic Obstructive Pulmonary Disease

Summary: primary objective: to evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate-or severe chronic obstructive pulmonary disease (copd) as measured by * annualized rate of acute moderate and severe copd exacerbation (aecopd) secondary objectives: to evaluate the effect of dupilumab administered every 2 weeks on * pre-bronchodilator forced expiratory volume in 1 second (fev1) over 12 weeks compared to placebo * health related quality of life, assessed by the change from baseline to week 52 in the st. george's respiratory questionnaire (sgrq) * pre-bronchodilator fev1 over 52 weeks compared to placebo * lung function assessments * moderate and severe copd exacerbations * to evaluate safety and tolerability * to evaluate dupilumab systemic exposure and incidence of anti-drug antibodies (ada)

approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up.

Eligibility criteria:
inclusion criteria: * participants with a physician diagnosis of copd who met the following criteria at screening: * current or former smokers with a smoking history of ≥10 pack-years. * moderate-to-severe copd (post-bronchodilator fev1/ forced vital capacity \[fvc\] ratio \ 30% and ≤70%). * medical research council (mrc) dyspnea scale grade ≥2. * patient-reported history of signs and symptoms of chronic bronchitis (chronic productive cough) for 3 months in the year up to screening in the absence of other known causes of chronic cough. * documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe within the year prior to inclusion. at least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ics)/long acting beta agonist (laba)/long acting muscarinic antagonist (lama) (or laba/lama if ics is contraindicated). moderate exacerbations were recorded by the investigator and defined as acute exacerbation of copd (aecopd) that required either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. one of the two required moderate exacerbations had to require the use of systemic corticosteroids. severe exacerbations were recorded by the investigator and defined as aecopd requiring hospitalization or observation \>24 hours in emergency department/urgent care facility. * background triple therapy (ics + laba + lama) for 3 months prior to randomization with a stable dose of medication for ≥1 month prior to visit 1; double therapy (laba + lama) allowed if ics was contraindicated. * evidence of type 2 inflammation: patients with blood eosinophils ≥300 cells/microliter at visit 1. exclusion criteria: * copd diagnosis for less than 12 months prior to randomization. * a current diagnosis of asthma or history of asthma according to the 2018 global initiative for asthma (gina) guidelines or other accepted guidelines. * significant pulmonary disease other than copd (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, churg-strauss syndrome etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts. * cor pulmonale, evidence of right cardiac failure. * treatment with oxygen of more than 12 hours per day. * hypercapnia requiring bi-level ventilation. * aecopd as defined in inclusion criteria within 4 weeks prior to screening, or during the screening period. * respiratory tract infection within 4 weeks prior to screening, or during the screening period. * history of, or planned pneumonectomy or lung volume reduction surgery. patients who were participating in the acute phase of a pulmonary rehabilitation program, ie, who started rehabilitation \<4 weeks prior to screening (note: patients in the maintenance phase of a rehabilitation program could be included). * diagnosis of α-1 anti-trypsin deficiency. the above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.